Consolidation is a series of cellular and system processes that stabilize a memory trace after the initial acquisition into a more permanent, stable memory. However, when that memory is recalled, it may again exist in a labile state. Reconsolidation refers to processes that return this labile memory trace back into a more permanent, stable memory. It has been clear for decades that stored information becomes amenable to change when retrieved. This is how we treat patients with anxiety disorders, by accessing the fear memory, changing it via treatment, with the updated less fearful memory becoming incorporated. It is also how patients relapse, when this memory becomes accessed and re-stored in a more fearful state during reconsolidation. An innovative preclinical study recently reported that providing a reminder of the fear 10 minutes prior to extinction training in humans decreased fear up to one year later (Schiller et al., 2010). For this pilot study, we will use virtual reality exposure therapy (VRE) for the methodological rigor that VRE allows. With VR, each research participant receives exactly the same exposure and testing as the others in the experimental session and there will be no exposure to the VR stimulus in between sessions or under different conditions. It is a nonpharmacological, safe, non-invasive intervention. We will use the virtual airplane for patients with the fear of flying (FOF) as: 1) it is a fairly discrete ear that is both serious in its interference yet expensive and difficult to treat in vivo; 2) there is limited exposure to the feared stimulus on a daily basis outside of the experimental conditions; 3) it is a clinical population with impairment and motivation for change yet without significant comorbidity; 4) a virtual airplane is available; 5) VRE FOF treatment is well documented in several controlled studies; 5) there is ample opportunity for the return of fear (relapse) as there tends to be limited exposure to actual flying for most patients; and 6) patients with the FOF are easy to recruit in Atlanta, the site of the proposed study and the world's busiest airport. We propose to treat 64 participants with VRE for the FOF and present a VR clip in the head mounted display 10 minutes prior to all VR exposure therapy sessions during this 3-year R34 pilot study. Participants will be randomly assigned to receive either a reminder of the feared stimulus (a VR clip of a virtual airplane taxiing and taking off) or a neutral cue (a VR clip of a virtual living room). The overall aim of this project is to determine if using a cue to recall the feared stimulus 10 minutes prior to exposure treatment sessions (and thus reactivate the memory trace) leads to less anxiety and return of fear in patients with an anxiety disorder compared to using a cue that does not recall the feared stimulus prior to treatment. The long term goals are to establish if targeting the reconsolidation of fear with a nonpharmacological, noninvasive reminder of the fear is effective for human clinical populations in reducing relapse (return of fear). PUBLIC HEALTH RELEVANCE: Targeting Memory Reconsolidation to Prevent the Return of Fear in a Pilot RCT Narrative We will test a brief, easy-to-implement manipulation (i.e., recall of a feared stimulus presented in virtual reality) that triggers the fear memory and presumably allows it to be changed in a way that prevents the fear from returning later (i.e., prevents relapse). We will use this recall before virtual reality exposure therapy for the fear of flying usng a virtual airplane so that every patient in the study will receive exactly the same exposure. If ths is successful, it is a very simple, safe, easy, inexpensive, efficient, nonpharmacological manipulation that could be used with all patients with anxiety disorders to help prevent the return of fear.